Elevated Hepatic Steatosis Research Articles

Multiparametric Magnetic Resonance Imaging and Magnetic Resonance Elastography to Evaluate the Early Effects of Bariatric Surgery on Nonalcoholic Fatty Liver Disease.

Bariatric surgery is the most effective treatment for morbid obesity and reduces the severity of nonalcoholic fatty liver disease (NAFLD) in the long term. Less is known about the effects of bariatric surgery on liver fat, inflammation, and fibrosis during the early stages following bariatric surgery. This exploratory study utilises advanced imaging methods to investigate NAFLD and fibrosis changes during the early metabolic transitional period following bariatric surgery. Nine participants with morbid obesity underwent sleeve gastrectomy. Multiparametric MRI (mpMRI) and magnetic resonance elastography (MRE) were performed at baseline, during the immediate (1 month), and late (6 months) postsurgery period. Liver fat was measured using proton density fat fraction (PDFF), disease activity using iron-correct T1 (cT1), and liver stiffness using MRE. Repeated measured ANOVA was used to assess longitudinal changes and Dunnett's method for multiple comparisons. All participants (Age 45.1 ± 9.0 years, BMI 39.7 ± 5.3 kg/m2) had elevated hepatic steatosis at baseline (PDFF >5%). In the immediate postsurgery period, PDFF decreased significantly from 14.1 ± 7.4% to 8.9 ± 4.4% (p = 0.016) and cT1 from 826.9 ± 80.6 ms to 768.4 ± 50.9 ms (p = 0.047). These improvements continued to the later postsurgery period. Bariatric surgery did not reduce liver stiffness measurements. Our findings support using MRI as a noninvasive tool to monitor NAFLD in patient with morbid obesity during the early stages following bariatric surgery.

Hepatocyte‐Specific Deletion of eNOS Impairs Mitochondrial Function and Exacerbates Hepatic Steatosis

IntroductionWhole body loss of endothelial nitric oxide synthase (eNOS) worsens hepatic mitochondrial function and exacerbates nonalcoholic fatty liver disease (NAFLD) development and progression. However, the precise role of eNOS in hepatocytes in the contribution to NAFLD has not been established. Here, we examine the effects of in vivo hepatocyte‐specific ablation of eNOS on hepatic steatosis and NAFLD susceptibility.MethodsHepatocyte‐specific eNOS knockout (eNOShep−/−) mice were generated by crossing homozygous eNOS floxed (eNOSfl/fl) mice on a C57/BL6J background with albumin‐Cre recombinase transgenic mice. At 10 weeks of age, male eNOSfl/fl and eNOShep−/− mice (n = 12–14) were fed a control diet (10% fat) for 16 weeks.ResultsBody weight, body fat, and food intake did not differ between eNOSfl/fl and eNOShep−/− mice. eNOShep−/− mice developed elevated histological hepatic steatosis and increased fasting serum insulin (~30%) compared to eNOSfl/fl mice (p<0.05), along with trends for elevations in serum liver enzymes AST and ALT (p<0.17). Elevated hepatic steatosis in eNOShep−/− was related to significant reductions (−50%) in hepatic mitochondrial fatty acid oxidation and ADP‐stimulated and maximal uncoupled hepatic mitochondrial respiration (p<0.05). However, hepatic citrate synthase activity, a marker of mitochondrial mass, was significantly elevated in eNOShep−/− mice compared to eNOSfl/fl mice (p<0.05), while protein content of oxidative phosphorylation complexes and peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) did not differ between groups. Furthermore, eNOShep−/− mice presented with significant reductions (p<0.05) in key proteins involved in mitophagy and autophagy including PTEN‐induced kinase 1 (PINK1) and phosphorylated Unc‐51 Like Autophagy Activating Kinase 1 (pUlk1/Ulk1) and tended to have significant reductions in BCL2/adenovirus E1B 19 kDa protein‐interacting protein 3 (BNIP3) compared to eNOSfl/fl mice.ConclusionHere we demonstrate for the first time that hepatocyte‐specific deletion of eNOS impairs hepatic mitochondrial function, reduces markers of autophagy/mitophagy, and exacerbates hepatic steatosis development. Further studies are necessary to determine the mechanisms by which deletion of eNOS regulates mitochondrial homeostasis.Support or Funding InformationVA Merit Grant I01BX003271‐01 (R.S.R.)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Amino Acid Metabolism is Altered in Adolescents with Nonalcoholic Fatty Liver Disease—An Untargeted, High Resolution Metabolomics Study

To conduct an untargeted, high resolution exploration of metabolic pathways that was altered in association with hepatic steatosis in adolescents. This prospective, case-control study included 39 Hispanic-American, obese adolescents aged 11-17years evaluated for hepatic steatosis using magnetic resonance spectroscopy. Of these 39 individuals, 30had hepatic steatosis ≥5% and 9 were matched controls with hepatic steatosis <5%. Fasting plasma samples were analyzed in triplicate using ultra-high resolution metabolomics on a Thermo Fisher Q Exactive mass spectrometry system, coupled with C18 reverse phase liquid chromatography. Differences in plasma metabolites between adolescents with and without nonalcoholic fatty liver disease (NAFLD) were determined by independent t tests and visualized using Manhattan plots. Untargeted pathway analyses using Mummichog were performed among the significant metabolites to identify pathways that were most dysregulated in NAFLD. The metabolomics analysis yielded 9583 metabolites, and 7711 with 80% presence across all samples remained for statistical testing. Of these, 478 metabolites were associated with the presence of NAFLD compared with the matched controls. Pathway analysis revealed that along with lipid metabolism, several major amino acid pathways were dysregulated in NAFLD, with tyrosine metabolism being the most affected. Metabolic pathways of several amino acids are significantly disturbed in adolescents with elevated hepatic steatosis. This is a novel finding and suggests that these pathways may be integral in the mechanisms of NAFLD.

Obesity and metabolic phenotypes (metabolically healthy and unhealthy variants) are significantly associated with prevalence of elevated C-reactive protein and hepatic steatosis in a large healthy Brazilian population.

Background. Among the obese, the so-called metabolically healthy obese (MHO) phenotype is thought to confer a lower CVD risk as compared to obesity with typical associated metabolic changes. The present study aims to determine the relationship of different subtypes of obesity with inflammatory-cardiometabolic abnormalities. Methods. We evaluated 5,519 healthy, Brazilian subjects (43 ± 10 years, 78% males), free of known cardiovascular disease. Those with <2 metabolic risk factors (MRF) were considered metabolically healthy, and those with BMI ≥ 25 kg/m2 and/or waist circumference meeting NCEP criteria for metabolic syndrome as overweight/obese (OW). High sensitivity C reactive protein (hsCRP) was measured to assess underlying inflammation and hepatic steatosis (HS) was determined via abdominal ultrasound. Results. Overall, 40% of OW individuals were metabolically healthy, and 12% normal-weight had ≥2 MRF. The prevalence of elevated CRP (≥3 mg/dL) and HS in MHO versus normal weight metabolically healthy group was 22% versus 12%, and 40% versus 8% respectively (P < 0.001). Both MHO individuals and metabolically unhealthy normal weight (MUNW) phenotypes were associated with elevated hsCRP and HS. Conclusion. Our study suggests that MHO and MUNW phenotypes may not be benign and physicians should strive to treat individuals in these subgroups to reverse these conditions.